The objectives of the proposed research are to delineate the genetic factors controlling arylsulfatase B expression in mammalian cells, to determine their linkage relations, and to study their mechanisms of action. Biochemical and genetic analyses of murine mutations which influence activities of arylsulfatase B and its isozymes in brain, kidney and liver will be utilized to accomplish these objectives. Arylsulfatase B will be purified from two inbred strains believed to share the same structural allele and from a third strain known to have a different allele. The biochemical properties, peptide profiles, and the amino acid and carbohydrate compositions of the respective enzymes will be compared to rule out significant structural variation between the enzymes from the strains sharing the same allele and to document structural variation between the isozyme from these strains and that of the third strain. Segregation of kidney and liver arylsulfatase B activities among progeny from crosses between strains sharing the same structural allele will be analyzed for effects of regulatory and temporal elements. Effects of the genes will be assessed by immunotitration and by a developmental approach. Cosegregation of arylsulfatase B, arylsulfatase B', and arylsulfatase A activities among progeny from informative crosses will be analyzed for evidence of common control, and structural probes will be utilized to explore the relationships between arylsulfatases B and B'. Methods will be developed to estimate rates of synthesis and turnover of arylsulfatase B.